| First Author | Mduff FK | Year | 2011 |
| Journal | Lab Invest | Volume | 91 |
| Issue | 9 | Pages | 1298-303 |
| PubMed ID | 21709672 | Mgi Jnum | J:175910 |
| Mgi Id | MGI:5287923 | Doi | 10.1038/labinvest.2011.96 |
| Citation | Mduff FK, et al. (2011) Determining the contribution of NPM1 heterozygosity to NPM-ALK-induced lymphomagenesis. Lab Invest 91(9):1298-303 |
| abstractText | Heterozygous expression of Nucleophosmin (NPM1) predisposes to hematological malignancies in the mouse and cooperates with Myc in lymphomagenesis. NPM1 is therefore regarded as a haploinsufficient tumor suppressor. Heterozygous loss of NPM1 occurs as a result of the t(2;5), which generates the oncogenic fusion tyrosine kinase, NPM-anaplastic lymphoma kinase (ALK), a molecule underlying the pathogenesis of anaplastic large cell lymphoma (ALCL). Given the aforementioned role of NPM1 as a tumor suppressor, we hypothesized that NPM1 heterozygosity would cooperate with NPM-ALK in lymphomagenesis. In the event, we observed no difference in tumor latency, incidence or phenotype in NPM-ALK-transgenic mice heterozygous for NPM1 relative to transgenic mice expressing both NPM1 alleles. We propose that although the t(2;5) simultaneously reduces NPM1 allelic dosage and creates the NPM-ALK fusion protein, the two events do not cooperate in the pathogenesis of ALCL in our mouse model. These data indicate that a tumor-suppressive role for NPM1 may depend on cellular and/or genetic context. |
